Efficient method for the synthesis of polysubstituted 2,6-dicyanoanilines by one-pot three-component tandem reaction of malononitrile with <Emphasis Type="Italic">α</Emphasis>,<Emphasis Type="Italic">β</Emphasis>-unsaturated imines

A facile and efficient one-pot synthesis of polysubstituted benzenes was achieved via the Michael addition of malononitrile with α,β-unsaturated imines and a sequential tandem reaction. This reaction generates polysubstituted 2,6-dicyanoanilines in high yields (15 examples, isolated yields of 57–91 %), and proceeds under mild reaction conditions (60°C, 10 min). In addition, a possible mechanism accounting for the reaction is proposed.     

The significance of a second adsorption phase with weakly adsorbed species for the calculation of the surface concentrations of a mixture: methanol–DME and methanol–ethene adsorption in SAPO-34

With the calorimetric (adsorption heat versus coverage) curve also measured together with the adsorption isotherm, the simultaneous use of both curves showed that there were two phases of adsorption in the adsorption of methanol, dimethyl ether, ethene and propane in SAPO-34. The dual-site Langmuir equation gave good fits to the adsorption data to support the interpretation that a second (type 2) adsorption phase occurred in the high-pressure region in addition to a first (type 1) adsorption phase on the acid sites at lower pressures. Adsorption experiments and calculations using binary gas mixtures showed that due to the existence of two types of adsorption, the multicomponent Langmuir isotherm equation (Langmuir competitive adsorption model) calculated incorrect surface concentrations when the concentrations were high. In contrast, the ideal adsorbed solution theory (IAST) calculated correct surface concentrations in the adsorption of mixtures.     

MgI2‐Mediated Chemoselective Cleavage of Protecting Groups: An Alternative to Conventional Deprotection Methodologies

The scope of MgI₂ as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports.     

Photosensitized Thymine Dimerization via Delocalized Triplet Excited States

A new mechanism of photosensitized formation of thymine (Thy) dimers is proposed, which involves generation of a delocalized triplet excited state as the key step. This is supported by chemical evidence obtained by combining one benzophenone and two Thy units with different degrees of freedom, whereby the photoreactivity is switched from a clean Paternò–Büchi reaction to a fully chemo‐, regio‐, and stereoselective [2+2] cycloaddition.     

Light‐Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy

Cancer treatment suffers from limitations that have a major impact on the patient’s quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.     

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

The interaction of the primary autoxidation products of cholesterol, namely 25‐ and 20ξ‐hydroperoxides, with the four principal cholesterol‐metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25‐hydroperoxide to the enzymes CYP27A1 and CYP11A1 induced well‐defined spectral changes while generating 25‐hydroxycholesterol as the major product. The 20ξ‐hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1 but glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides. A P450 hydroperoxide‐shunt reaction is proposed, where the hydroperoxides serve as both donor for reduced oxygen and substrate. CYP27A1 was shown to mediate the reduction of cholesterol 25‐hydroperoxide to 25‐hydroxycholesterol, a role of potential significance for cholesterol‐rich tissues with high oxidative stress. CYP27A1 may participate in the removal of harmful autoxidation products in these tissues, while providing a complementary source of 25‐hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry.